Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in the tumor immune microenvironment (TIME) across different TNBC molecular subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling and bioinformatic analyses to classify TNBC samples into molecular subtypes, as well as immunohistochemistry and cell deconvolution methods to characterize the TIME. Results revealed significant heterogeneity in immune cell composition among TNBC subtypes, with the immunomodulatory (IM) subtype demonstrating robust immune infiltration, composed mainly of adaptive immune cells along with an increased density of CTLA-4+ and PD-1+ TILs, high PD-L1 tumor cell expression, and upregulation of FOXP3+ Tregs. A more immunosuppressive TIME with a predominance of innate immune cells and lower levels of tumor-infiltrating lymphocytes (TILs) was observed in luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, the TIME was mainly composed of innate immune cells, with a high number of M2 tumor-associated macrophages (TAMs), while the BL and M tumors displayed poor adaptive and innate immune responses, indicating an “immune-cold” phenotype. Differential activation of signaling pathways, genomic diversity, and metabolic reprogramming were identified as contributors to TIME heterogeneity. Understanding this interplay is crucial for tailoring therapeutic strategies, especially regarding immunotherapy.
三阴性乳腺癌（TNBC）具有不同的分子亚型，各亚型具备独特的生物学和临床特征。本系统综述旨在筛选并分析探讨不同TNBC分子亚型间肿瘤免疫微环境（TIME）差异的研究文献。经筛选，共纳入六项符合标准的研究，这些研究利用基因表达谱分析和生物信息学方法对TNBC样本进行分子亚型分类，并采用免疫组织化学和细胞反卷积技术来表征TIME。结果显示，TNBC各亚型间的免疫细胞组成存在显著异质性：免疫调节型（IM）亚型表现出显著的免疫浸润，主要由适应性免疫细胞构成，同时CTLA-4+和PD-1+肿瘤浸润淋巴细胞（TILs）密度增加，肿瘤细胞PD-L1高表达，且FOXP3+调节性T细胞（Tregs）上调；而在管腔雄激素受体型（LAR）肿瘤中，观察到更具免疫抑制性的TIME，以先天性免疫细胞为主，且TILs水平较低；间充质干细胞样（MSL）肿瘤的TIME主要由先天性免疫细胞构成，含有大量M2型肿瘤相关巨噬细胞（TAMs）；而基底样（BL）和间充质（M）型肿瘤则表现出较弱的适应性和先天性免疫应答，呈现“免疫冷”表型。研究还发现，信号通路的差异激活、基因组多样性以及代谢重编程是导致TIME异质性的重要因素。深入理解这种相互作用对于制定个体化治疗策略，尤其是在免疫治疗方面，至关重要。
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